Study to Characterize Absorption, Distribution, Metabolism and Excretion of 14C PF-06651600 and to Evaluate the Absolute Oral Bioavailability and Fraction Absorbed of PF-06651600.

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: 14C-PF-06651600; Drug: 14C-PF-06651600 IV; Drug: PF-06651600

• Registration Number: NCT03929510
• Lead Sponsor: Pfizer

Brief Summary

This study will investigate the absorption, distribution, metabolism and excretion (ADME) of 14C PF-06651600 and characterize plasma, fecal and urinary radioactivity and identify any metabolites, if possible, of 14C PF-06651600 in humans.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-17
• Study Start: 2019-04-23
• Study First Submitted QC: 2019-04-25
• Study First Posted: 2019-04-29
• Status Verified: 2019-07
• Primary Completion: 2019-07-05
• Study Completion: 2019-07-05
• Last Update Submitted: 2019-07-23
• Last Update Posted: 2019-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

• Male participants who are healthy as determined by medical evaluation including a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) measurement, 12 lead ECG, and clinical laboratory tests.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

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Exclusion Criteria

• Known immunodeficiency disorder, including positive serology for human immunodeficiency virus (HIV) at screening, or a first degree relative with a hereditary immunodeficiency.
• Infection with hepatitis B or hepatitis C viruses.
• Participants with selected acute or chronic infections or infection history.
• Participants have a known present or a history of malignancy other than a successfully treated or excised non metastatic basal cell or squamous cell cancer of the skin.
• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening.
• Use of tobacco/nicotine containing products within 3 months prior to dosing or positive urine cotinine test.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Period A	14C-PF-06651600	Single oral dose of 200 mg 14C labeled PF-06651600 containing approximately 300 nCi 14C (ie, radiolabeled PF 06651600).
Period B	14C-PF-06651600 IV	Single oral dose of 200 milligrams (mg) unlabeled PF-06651600 followed at time of peak plasma concentration (Tmax) by an Intravenous (IV) dose of 60 micrograms.14C -PF-06651600 containing approximately 300 nCi 14C (ie, radiolabeled PF-06651600).
Period B	PF-06651600	Single oral dose of 200 milligrams (mg) unlabeled PF-06651600 followed at time of peak plasma concentration (Tmax) by an Intravenous (IV) dose of 60 micrograms.14C -PF-06651600 containing approximately 300 nCi 14C (ie, radiolabeled PF-06651600).

Primary Outcome Measures

Name	Time	Method
Mass Balance: Cumulative recovery (%) of radioactivity in urine	from time zero to the time of last measurable concentration following oral administration of 14C PF-06651600 microtracer dose up to day 24	Cumulative recovery (%) of radioactivity in urine.
Mass Balance: Cumulative recovery (%) of radioactivity in feces	from time zero to the time of last measurable concentration following oral administration of 14C PF-06651600 microtracer dose up to day 24	Cumulative recovery (%) of radioactivity in feces

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Baseline (Day 0) up to Day 24	Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) obtained from each participant. Clinical significance of vital signs was determined at the investigator's discretion.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities	Baseline (Day 0) up to Day 24	Laboratory parameters include: hematological and chemical parameters
Amount (% of the administered dose) of major metabolites of PF-06651600 in urine	Hour 0 up to 312 hours post-dose.
AUClast	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Area under the plasma concentration time profile from time 0 to time of the last quantifiable concentration (Clast)
AUCinf	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Area under the plasma concentration time profile from time 0 to infinity
Tmax	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Time for Cmax
CL (IV)	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed.
Vz/F	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Apparent volume of distribution following oral administration
Total 14C_Urine_PO	Pre-dose, Day1, day 2, day 3, day 4, day 5, day 6 and day 7 post-dose	Total radioactivity excreted into the urine from time zero to the time of last measurable concentration following oral administration of 14C PF 06651600 microtracer dose
Amount (% of the administered dose) of major metabolites of PF-06651600 in plasma	Hour 0 up to 312 hours post-dose.
Amount (% of the administered dose) of major metabolites of PF-06651600 in feces	Hour 0 up to 312 hours post-dose.
t1/2	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
CL/F (oral)	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). Clearance obtained after intravenous infusion dose (apparent clearance) is influenced by the fraction of the dose absorbed.
Cmax	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Maximum plasma concentration
Vss	Pre-dose, 0.25. 0.5, 1, 1.5, 2, 3.5, 4.5, 6.5, 8.5, 12.5, 24, 48, 72, 96 hours post-dose	Steady state volume of distribution following IV infusion
Total 14C_Urine_IV	Pre-dose, Day1, day 2, day 3, day 4, day 5, day 6 and day 7 post-dose	Total radioactivity excreted into the urine from time zero to the time of last measurable concentration following IV administration of 14C PF 06651600 microtracer dose
AE	Baseline (Day 0) up to 90 days after last dose of study medication	Number of subjects and number of AEs which are any untoward medical occurrence regardless of attribution to study drug in a participant who received study drug.
Number of participants with clinically significant changes to the physical examination	Baseline (Day 0) up to Day 24	clinically significant changes to the physical examination

Trial Locations

Locations (2)

PRA Health Sciences Utrecht; 🇳🇱 Utrecht, Netherlands

PRA Health Sciences; 🇳🇱 Groningen, Netherlands